Papers by Darunee Hongwiset
Structure–Activity Studies on Suramin Analogues as Inhibitors of NAD+-Dependent Histone Deacetylases (Sirtuins)
ChemMedChem, Oct 8, 2007
Suramin is a symmetric polyanionic naphthylurea originally used for the treatment of trypanosomia... more Suramin is a symmetric polyanionic naphthylurea originally used for the treatment of trypanosomiasis and onchocerciasis. Suramin and diverse analogues exhibit a broad range of biological actions in vitro and in vivo, including, among others, antiproliferative and antiviral activity. Suramin derivatives usually target purinergic binding sites. Class III histone deacetylases (sirtuins) are amidohydrolases that require nicotinamide adenine dinucleotide (NAD+) as a cofactor for their catalytic mechanism. Deacetylation of the target proteins leads to a change in conformation and alters the activity of the proteins in question. Suramin was reported to inhibit human sirtuin 1 (SIRT1). We tested a diverse set of suramin analogues to elucidate the inhibition of the NAD+‐dependent histone deacetylases SIRT1 and SIRT2 and discovered selective inhibitors of human sirtuins with potency in the two‐digit nanomolar range. In addition, the structural requirements for the binding of suramin derivatives to sirtuins were investigated by molecular docking. The recently published X‐ray crystal structure of human SIRT5 in complex with suramin and the human SIRT2 structure were used to analyze the interaction mode of the novel suramin derivatives.
Cogent Chemistry, 2018
Two known furanocoumarins, namely, 6ˊ, 7ˊ-dihydroxybergamottin (1) and oxypeucedanin hydrate (2),... more Two known furanocoumarins, namely, 6ˊ, 7ˊ-dihydroxybergamottin (1) and oxypeucedanin hydrate (2), were isolated from Kaffir lime (Citrus hystrix DC) fruit peel using an assay of nitric oxide scavenging effect-guided fractionation. The inhibitory activities of isolated coumarins on the production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were studied in mouse macrophages RAW264.7 cells, whereas their inhibitory effect on cyclooxygenase-2 (COX-2) production was investigated using HT-29 and HCT116 cells. The results demonstrated that 1 inhibited lipopolysaccharideinterferon gamma-induced NO and iNOS production in RAW264.7 cells and COX-2 production in HT-29 and HCT116 cells with IC 50
Journal of Medicinal Chemistry, Oct 1, 2005
Synthetic procedures and compound monographs S2-S11 Elemental analysis data (CHN) S12-S13 S2 4-Et... more Synthetic procedures and compound monographs S2-S11 Elemental analysis data (CHN) S12-S13 S2 4-Ethyl-3-nitro-benzoic acid was synthesized according to Fahim and Fleifel. 39
Proceedings of the 3rd International Conference on Computation for Science and Technology, 2015
Polyphenols are widely presented in plants and dietary supplements. The beneficial effects of the... more Polyphenols are widely presented in plants and dietary supplements. The beneficial effects of these compounds have been demonstrated, including the prevention of cardiovascular diseases, osteoporosis, neurogenerative diseases and diabetes. From previous studies, polyphenols showed the inhibitory effect on cytochrome P450 2C9 (CYP2C9) resulting in clinically significant of herb-drug interactions. CYP2C9 is involved in the biotransformation of various therapeutic drugs, including tolbutamide, phenytoin and warfarin. Co-administration of polyphenols with drugs that are metabolized through CYP2C9 can cause therapeutic failures or adverse events from the co-administered drugs. This study aimed to identify the interactions between polyphenols and CYP2C9 by using molecular docking program, CDOCKER, to calculate binding energy. Ten polyphenols used in this study were naringenin, chrysin, apigenin, luteolin, acacetin, galangin, kaempferol, quercetin, myricetin and isorhamnetin. The results showed that polyphenols can bind to the same binding site as flurbiprofen, which was used as the ligand in the x-ray crystal structure of the CYP2C9-flurbiprofen complex (1R9O) and the amino acid Phe100,
Synthesis of N-acyl-N'-arylurea derivatives
Evaluation of Tonic Potential of Kamlang Suea Khrong Crude Drugs Originated From Three Medicinal Plants
Journal of Medicinal Chemistry, Dec 1, 2005
Benzoxazole derivatives R 0230 Synthesis and Structure-Activity Relationship of Novel Benzoxazole... more Benzoxazole derivatives R 0230 Synthesis and Structure-Activity Relationship of Novel Benzoxazole Derivatives as Melatonin Receptor Agonists.-The constrained cyclopropane moiety in the side chain of previously discovered benzoxazol derivatives with high binding affinity toward human MT1 and MT2 receptor subtypes is replaced by a conformationally flexible alkyl side chain. The terminal amide moiety and the C2-position of the benzoxazole ring are the regions of choice with regard to structure-activity relationships. The novel ligands (VIIa) and (VIIb) are identified as melatonin receptor agonists and (VIIc) as a highly potent MT1 ligand with moderate receptor selectivity.-(SUN*, L.-Q.;
Structure–Activity Studies on Suramin Analogues as Inhibitors of NAD+-Dependent Histone Deacetylases (Sirtuins)
ChemMedChem, 2007
Suramin is a symmetric polyanionic naphthylurea originally used for the treatment of trypanosomia... more Suramin is a symmetric polyanionic naphthylurea originally used for the treatment of trypanosomiasis and onchocerciasis. Suramin and diverse analogues exhibit a broad range of biological actions in vitro and in vivo, including, among others, antiproliferative and antiviral activity. Suramin derivatives usually target purinergic binding sites. Class III histone deacetylases (sirtuins) are amidohydrolases that require nicotinamide adenine dinucleotide (NAD(+)) as a cofactor for their catalytic mechanism(.) Deacetylation of the target proteins leads to a change in conformation and alters the activity of the proteins in question. Suramin was reported to inhibit human sirtuin 1 (SIRT1). We tested a diverse set of suramin analogues to elucidate the inhibition of the NAD(+)-dependent histone deacetylases SIRT1 and SIRT2 and discovered selective inhibitors of human sirtuins with potency in the two-digit nanomolar range. In addition, the structural requirements for the binding of suramin derivatives to sirtuins were investigated by molecular docking. The recently published X-ray crystal structure of human SIRT5 in complex with suramin and the human SIRT2 structure were used to analyze the interaction mode of the novel suramin derivatives.
Quantitation of lupeol from stem bark extract of Betula alnoides Buch.-Ham. ex D.Don by two validated RP-HPLC and TLC-densitometric methods
Journal of Liquid Chromatography & Related Technologies, 2021
Solubility and stability are two key aspects of any successful formulation for curcumin beverage ... more Solubility and stability are two key aspects of any successful formulation for curcumin beverage development. In the present study, the effect of polysorbate on the solubility of curcumin in aqueous solution with or without the autoclave treatment was studied. The remarkable effect of the autoclave treatment on enhancing the solubility was confirmed. Among polysorbate 20, 60 and 80, polysorbate 20 exhibited the highest solubility of approximately 6 mg/ml in 20% aqueous solution by the autoclave treatment, while the solubility was approximately 4 mg/ml in polysorbate 60 and 80, prepared under the same condition. Without the autoclave treatment, the solubility in 20% aqueous solutions of polysorbate 20, 60 and 80 was 2.7, 3.4 and 3.4 mg/ml, respectively. The stability of curcumin was obviously improved a lot by applying the micelle formation with polysorbate. However, the remarkable decomposition of curcumin at 30 and 40°C was observed over a few weeks. Dynamic light scattering study ...
Pharmacokinetics and Analytical Determination of Acyclovir in Asian Elephant Calves (Elephas maximus)
Veterinary and Animal Science
International Journal of Pharmacy and Pharmaceutical Sciences, 2014
Objective: The present study was aimed to investigate the physicochemical properties, chemical ch... more Objective: The present study was aimed to investigate the physicochemical properties, chemical characterization and skin moisturizing effect of the mucilages extracted from Hibiscus rosa-sinensis (HR), and H. mutabilis (HM). Methods: The HR and HM leaves were extracted with distilled water to obtain their mucilages. Then dried and powdered. The physicochemical properties of the mucilage powders, including pH value, swelling index, loss on drying, solubility, total ash, acid-insoluble ash and carbohydrate content were evaluated. The polysaccharides were isolated from the mucilages and purified by DEAE-650M column and identified the sugar unit constituents by acid hydrolysis, followed by TLC and HPAEC analyses. The short-term moisturizing effect of the mucilages was determined on pig skin using Corneometer ® . Results: The yield of HR and HM mucilages was 21% and 15% w/w. Each of mucilage showed the specific physicochemical properties. The main component of HR and HM mucilages was aci...
Spezielle carbonylbisimino verbindungen zur verwendung als p2y11 rezeptor agonisten in der behandlung von immunerkrankungen
To determine the pharmacokinetics of 8-mg galantamine prolonged-release capsules under fed and fa... more To determine the pharmacokinetics of 8-mg galantamine prolonged-release capsules under fed and fasting conditions. A randomised, open-label, single-dose, two-treatment, two-period, two-sequence, parallel design of the administration of 8-mg galantamine hydrobromide prolonged-release capsules under fed and fasting conditions in 52 healthy Thai volunteers. Each subject was randomly assigned to receive a single oral dose of galantamine under fed or fasting conditions with a 7-day washout period. Blood samples were collected between 0.0 and 48.0 h following drug administration. LC-MS/MS was used for the quantitation of galantamine in plasma. Pharmacokinetics parameters were analysed including Cmax, Tmax, T1/2, ke, AUC0-48h, and AUC0-inf. 46 subjects completed the present study. The mean Cmax values were 41.95 + 10.05 ng/mL and 25.96 + 4.18 ng/mL, and the mean AUC0-48h values were 599.45 + 159.54 and 503.47 + 79.62 ng.h/mL under fed and fasting conditions, respectively. The mean AUC0-inf...
Evidence-Based Complementary and Alternative Medicine
Background. Cissus quadrangularis Linn. (CQ) is a medicinal plant with good evidence for the trea... more Background. Cissus quadrangularis Linn. (CQ) is a medicinal plant with good evidence for the treatment of hemorrhoids, listed in the Thai National List of Herbal Products in the oral dosage form. Acmella paniculata (Wall ex. DC.) R. K. Jansen. (AP) is a medicinal plant with a local anesthetic effect. Objective. To investigate the potential of rectal suppositories containing CQ and AP extracts to alleviate symptoms of hemorrhoids compared with the commercialized rectal suppository containing hydrocortisone and cinchocaine. Materials and Methods. Hemorrhoid outpatients (n = 105) with different severity grades (I, II, or III) from eight hospitals in northern Thailand were included in this study. Hemorrhoid severity was graded by proctoscopy associated with either anal pain or bleeding related to hemorrhoids or both. The patients were randomly allocated to two groups: CQ-AP group (n = 52) or the commercialized rectal suppository group (n = 53). One suppository was rectally administered ...
Verification of Thai ethnobotanical medicine “Kamlang Suea Khrong” driven by multiplex PCR and powerful TLC techniques
PLOS ONE
Kamlang Suea Khrong (KSK) crude drug, a traditional Thai medicine used for oral tonic and analges... more Kamlang Suea Khrong (KSK) crude drug, a traditional Thai medicine used for oral tonic and analgesic purposes, is obtained from three origins: the inner stem bark of Betula alnoides (BA) or the stems of Strychnos axillaris (SA) or Ziziphus attopensis (ZA). According to the previous reports, SA contains strychnine-type alkaloids that probably cause poisoning; however, only organoleptic approaches are insufficient to differentiate SA from the other plant materials. To ensure the botanical origin of KSK crude drug, powerful and reliable tools are desperately needed. Therefore, molecular and chemical identification methods, DNA barcoding and thin-layer chromatography (TLC), were investigated. Reference databases, i.e., the ITS region and phytochemical profile of the authentic plant species, were conducted. In case of molecular analysis, multiplex polymerase chain reaction (PCR) based on species-specific primers was applied. Regarding species-specific primers designation, the suitability ...
Molecular Modeling for a Comparative Analysis of Interactions Between 2LTRZFP and 2-LTR-Circle Junctions
International Journal of Peptide Research and Therapeutics
In eukaryotes, one of the most often noticed DNA-binding motifs are Cys2His2 zinc finger proteins... more In eukaryotes, one of the most often noticed DNA-binding motifs are Cys2His2 zinc finger proteins which have been extensively utilized as a framework for designing novel DNA-binding proteins. In this study, the conformational change, and binding stability, affinity and interactions of the 2LTRZFP–HIV-1 2-LTR-circle junction complexes were successfully reproduced with MD simulations, MM-PBSA/GBSA and binding mode analyses. The binding free energies were obtained, and it was found that the calculated binding free energy of Zif1 is lower than Zif2 and together with pharmacophore modeling, these binding results indicate strong affinity of 2LTRZFP for the DNA. Mutants of 2LTRZFP were analyzed. The computed energies provided proof for a relationship between the binding free energy and total electrostatic interaction energy. The mutation in a key amino acid (Glu81Tyr) of the finger 3 in position 6 showed increased binding energy to the DNA. The result agrees with our previous study which showed that the HIV-1 IN may be hindered by the 2LTRZFP. The obtained results may assist in the design of ZFPs depended on the 2-LTR-circle junctions inhibition mechanism.
Journal of Veterinary Medical Science
Note Wildlife Science Case report: Successful treatment of elephant endotheliotropic herpesvirus ... more Note Wildlife Science Case report: Successful treatment of elephant endotheliotropic herpesvirus infection in an Asian elephant (Elephas maximus) calf by oral acyclovir medication Siripat KHAMMESRI 1),2) , Yaoprapa Mathura 2) , Khajohnpat Boonprasert 2) , Chadarat Ampasavate 3) , Darunee Hongwiset 3) , Janine L Brown 2), 4) and Chatchote Thitaram 2), 5)*
Cogent Medicine
A rapid, sensitive and reliable LC-MS/MS method for the determination of galantamine in plasma wa... more A rapid, sensitive and reliable LC-MS/MS method for the determination of galantamine in plasma was developed and validated for the pharmacokinetic study of galantamine hydrobromide 8 mg prolonged-release capsules. The plasma sample was prepared by simple liquid-liquid extraction with dichloromethane. Chromatographic separation was performed on a Hypurity C4 (150 x 4.6 mm, particle size 5.0 µm) using isocratic acetonitrile: 10 mM ammonium formate (90:10) as a mobile phase at a flow rate of 0.8 mL/ min. Galantamine was detected by mass spectrometry using the electrospray ion source in the selected reaction monitoring mode. Carbamazepine was used as an internal standard (IS). The extraction recovery was 105.45-111.84% for galantamine and 107.35% for IS. Linearity was found within the calibration range of 0.39-62.5 ng/mL. The intra-day and inter-day accuracy were achieved with the mean concentrations of the quality control samples as 91.92-100.97% and 94.29-102.07%, respectively. The intra-ABOUT THE AUTHOR Dr. Darunee Hongwiset completed her doctoral degree from Heinrich-Heine-Universität Düsseldorf, Germany, after receiving M.S. in Pharmaceutical Chemistry from Chulalongkorn University (CU) and B.Pharm. from Chiang Mai University (CMU). Associated Prof. Dr. Songwut Yotsawimonwat completed his B.Pharm., M. S. and Ph.D. from CMU. He is well versed in pharmaceutical technology research. Associated Prof. Chokchai and Assistance Prof. Dr. Chuleegone Sornsuvit finished his and her graduation from Mahidol University in the field of Pharmaceutical Care. Miss Saowarunee Sangsrijan graduated from Faculty of Sciences, CMU. She is an expert in bioanalysis and bioequivalence study. We are staffs in Faculty of Pharmacy, CMU, and also in Pharmacy Service Center. We are interested in pharmaceutical development and bioanalytical study, especially in bioavailability and bioequivalence study.
Furanocoumarins from Kaffir lime and their inhibitory effects on inflammatory mediator production
Cogent Chemistry
Abstract Two known furanocoumarins, namely, 6ˊ, 7ˊ-dihydroxybergamottin (1) and oxypeucedanin hyd... more Abstract Two known furanocoumarins, namely, 6ˊ, 7ˊ-dihydroxybergamottin (1) and oxypeucedanin hydrate (2), were isolated from Kaffir lime (Citrus hystrix DC) fruit peel using an assay of nitric oxide scavenging effect-guided fractionation. The inhibitory activities of isolated coumarins on the production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were studied in mouse macrophages RAW264.7 cells, whereas their inhibitory effect on cyclooxygenase-2 (COX-2) production was investigated using HT-29 and HCT116 cells. The results demonstrated that 1 inhibited lipopolysaccharide-interferon gamma-induced NO and iNOS production in RAW264.7 cells and COX-2 production in HT-29 and HCT116 cells with IC50 values of 16.16 ± 1.08, 18.63 ± 1.42, 18.19 ± 0.95 and 17.53 ± 0.88 µg/mL, respectively; 2 showed IC50 values of 18.23 ± 1.25, 22.54 ± 1.56, 22.27 ± 1.14 and 23.24 ± 1.05 µg/mL, respectively. Additionally, the positive control curcumin exhibited these activities with IC50 values of 12.52 ± 0.63, 15.55 ± 1.34, 14.29 ± 0.58 and 16.14 ± 0.65 µg/mL, respectively. The inhibitory effect of 1 on the production of iNOS and COX-2 was significantly stronger than that of 2. This study indicated that furanocoumarins from Kaffir lime fruit peels have potency for further development as an anti-inflammatory drug.
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Papers by Darunee Hongwiset